The invention relates to peptides with 3-15 amino acids which function as agonists and/or inhibitors in amyloid formation and/or toxicity and which can be therefore used in various related clinical pictures.
New strategies and active agents for the therapy and diagnosis of the above-mentioned amyloid illnesses are being researched world-wide. However, there is still no means of treating these illnesses with medicines/pharmaceuticals. According to predominant expert opinion, certain amyloid proteins, which are specific to each illness, are causally responsible for the occurrence of amyloid illnesses because of their amyloid genesis or aggregation. The mechanism for amyloid genesis and the associated cell death (cytotoxicity) in these illnesses is widely unknown and correspondingly, highly specific inhibitors have hence not been identified. Pharmaceuticals for treating amyloid illnesses on the basis of such inhibitors have therefore also not been developed.
In exactly the same way, the protein-chemical, technical-analytical problems, which are caused by amyloid formation, (formation of insoluble protein aggregates, so-called amyloid structures) have up to now not permitted the analysis of amyloid formation. This has contributed to the fact that the mechanism for amyloid formation is still widely unexplained. For analysing the formation of amyloids, constructive diagnostic methods (fast in vitro tests for evaluating the amount, duration and quality of the amyloid structures) still therefore do not exist either. For example, a diagnosis for Alzheimer""s can only be performed symptomatically (increasing forgetfulness or similar) or post mortem. Reliable blood tests, for example, cannot be performed during the lifetime of the patient.
On this basis it is therefore the object of the invention to propose appropriate peptides, which can function as agonists and/or inhibitors of amyloid formation and/or cytotoxicity.
According to the invention, peptides with 3-15 amino acids are proposed, which contain at least the active sequence GA. It has been shown, that these peptide molecules function as inhibitors and/or agonists of those amyloid peptides/proteins, which cause the amyloid illnesses Alzheimer""s disease, Type II diabetes mellitus and spongiform encephalopathies (Creutzfeld Jacob disease, scrapie, BSE). The peptide molecules according to the invention are in a position to inhibit the amyloid genesis or aggregation of the amyloid peptides/proteins of amyloid peptide or xcex2-AP (in Alzheimer""s disease), amyline/IAPP (in Type II diabetes mellitus) and prion protein (in spongiform encephalopathies). When inhibition of the amyloid genesis of illness-inducing peptides/proteins is achieved, the cytotoxic effect, which is caused by aggregation of xcex2-AP, amyline/IAPP or prion protein, on tissue cells is inhibited.
The invention offers the following advantages relative to the state of the art:
Simple chemosynthesis to a high degree of purity, and use, according to current methods, of fixed phase peptide synthesis (the peptides described here are shorter, as a rule, than the potential inhibitors described up till now and consist of only one type of chemical component [=amino acids]).
high biological stability, which can be increased even more by the simple chemical inclusion of unnatural amino acids.
broad biological and therefore potentially therapeutic applicability (the high homology level between the corresponding sequences of amyloid-forming peptides/proteins makes possible the overlapping application of inhibitors in all three illnesses).
few side-effects and little antigenicity when used as a therapeutic (the peptides, on the basis of their small size, have a small tendency to induce immune reactions in the patient); other inhibitor candidates which are described in the literature (see above antibodies or higher molecular serum components) are approx. 200-300 times larger than the peptides which are described here.
high biological activity in vitro and thus high predictable biological activity in vivo.
thus high predictability of therapeutic application.